Andrew Mente, on behalf of the PURE investigators Fruit, vegetable and legume intake and CVD and deaths: the Prospective Urban Rural Epidemiology (PURE) study of 135,335 people in 18 countries Andrew Mente, on behalf of the PURE investigators

Duality of Interests None to declare with regards this presentation

Background - Few data from South America, Middle East, Africa and Dietary guidelines recommend at least 5 daily servings (≥400 g) of fruits, vegetables and legumes Associated with lower risk of CVD and mortality, but could be influenced by health seeking behaviors - Few data from South America, Middle East, Africa and South Asia; Most data from N Amer, Europe, China, Japan Recommendations do not differentiate between raw and cooked vegetable intake

Aims To assess the association between fruit, vegetable and legume consumption and cardiovascular disease and mortality in 135,335 individuals in 18 countries

Study Methods Design: Prospective cohort study Population: Unbiased selection from general population in 667 urban/rural communities in 18 countries N=135,335; aged 35-70 years, without CVD at baseline Exposure: Country-specific, validated food frequency questionnaires Covariates: Demographics, other lifestyle, health history, center Outcomes: Major CVD (CV death and nonfatal MI, stroke, and heart failure) (n=4784), using standardized definitions; total mortality (n=5796) Follow-up: Median 7.4 years

PURE: 135,335 from 667 communities in 18 Phase 1 countries from 5 continents Target: 200,000 people PURE is unique because it is 1) large, 2) prospective, 3) covers 5 continents representing broad patterns of diet globally

Countries Geographic region Countries N South Asia Bangladesh, India, Pakistan 29,560 China 42,152 Southeast Asia Malaysia 10,038 Africa South Africa, Zimbabwe 4,558 North America Canada, Poland, Sweden, 14,916 Middle East Iran, Occupied Palestinian Territory, Turkey, United Arab Emirates 11,485 South America Argentina, Brazil, Chile, Colombia 22,626 Overall 135,335 This slide shows the list of countries by geographic region, which include…

Phase-1 participants included in these analyses N=157,543 participants from 18 countries Did not complete an FFQ (6.9%) N=146,646 completed FFQ Implausible values (1.9%) Energy <500 or >5000 kcal/d N=143,934 Missing follow-up (0.9%) N=142,704 Baseline CVD (5.2%) N=135,335

Statistical Methods Studied time to events Multivariable Cox frailty analysis with random intercepts to account for correlation of observation within centers Adjusted for: Age, sex, urban/rural location Education, smoking, physical activity, diabetes Energy intake, meats, bread & cereal When reporting fruit, adjust for vegetables, and vice-versa

Mean fruit, vegetable and legume intake by region Overall average intake is 4 servings / day >5 in 3 regions – A Amer/Eur, S Amer, and M East Rest of the countries consume 3 servings per day Legume intake is modest in each region except South Asia

Risk of mortality by total fruit, veg & legume intake Servings/day N No. of deaths (%) Age & sex adj. Full adjusted <1 /day 9082 736 (8.1%) 1.0 (ref) 1 to <2 /day 19036 1371 (7.2%) 0.92 (0.84-1.01) 1.01 (0.91-1.12) 2 to <3 /day 35128 1529 (4.4%) 0.81 (0.74-0.89) 0.91 (0.82-1.01) 3 to <4 /day 24485 772 (3.2%) 0.65 (0.58-0.74) 0.78 (0.69-0.88) 4 to <5 /day 14849 468 (3.2%) 0.83 (0.72-0.95) 5 to <6 /day 9790 286 (2.9%) 0.62 (0.53-0.71) 0.78 (0.66-0.91) 6 to <8 /day 6945 198 (2.9%) 0.63 (0.54-0.75) 0.84 (0.70-1.00) 7 to <8 /day 4857 131 (2.7%) 0.61 (0.50-0.74) 0.83 (0.67-1.02) >8 /day 11163 305 (2.7%) 0.58 (0.50-0.74) 0.81 (0.68-0.96) P for trend <0.0001 0.0001 There is a graded association with lower risk all the way to >8 serving/day If fully adjusted, the maximum benefit is achieved by 3-4 servings and then risk appears to be constant Therefore, 3-4 servings is associated with maximum benefit After adjustment, the effect sizes are halved, - suggests that there may be residual confounding in estimating association between fruit, veg and legume intake versus mortality

Risk of mortality and major CVD by total fruit, vegetable and legume intake (servings/day) HR (95% CI) Intake HR (95% CI) 0.6 0.8 1 1.2 P-trend=0.0001 0.6 0.8 1 1.2 1.4 P-trend=0.13 Figure shows risk of mortality and CVD by intake, after MV adjustment for confounders Mortality figure – significant associations with mortality, with a minimal intake of 3-4 serv achieving a Signiant lowering risk of mortality. CVd figure – no significant association seen with CVD, although there may be a trend. for lower risk

Risk of mortality and major CVD by fruit intake (servings) HR (95% CI) Intake HR (95% CI) 0.6 0.8 1 1.2 P-trend<0.0001 0.6 0.8 1 1.2 P-trend=0.11 Consistent with lower mortality BUT No significant association with CVD , perhaps a lower risk with >3 servings/day

Risk of mortality and major CVD by vegetable intake (servings/day) HR (95% CI) Intake HR (95% CI) 0.6 0.8 1 1.2 P-trend=0.12 0.8 1 1.2 1.4 P-trend=0.38 a nonsignificant trend with lower mortality No association with major CVD

Mean raw and cooked vegetable intake by region Excluding China (N=42,152) Overall, average intake of fruit & veg is 2 servings per day. N Amer/Eur consume more raw than cooked vegetables, Conversely, other regions consume more cooked vegetables, particularly Africa, S Asia and SE Asia where is mostly cooked vegs.

Risk of mortality and major CVD by raw vegetable intake (servings) HR (95% CI) Intake HR (95% CI) 0.6 0.8 1 1.2 P-trend=0.0004 0.6 0.8 1 1.2 P-trend=0.27 Excluding China

Risk of mortality and major CVD by cooked vegetable intake (servings) HR (95% CI) Intake HR (95% CI) 0.6 0.8 1 1.2 P-trend=0.011 0.8 1 1.2 1.4 P-trend=0.085 Excluding China

Risk of mortality and major CVD by legume intake (servings) HR (95% CI) Intake HR (95% CI) 0.6 0.8 1 1.2 P-trend=0.0013 0.6 0.8 1 1.2 P-trend=0.19 Sig association with legumes Suggests legumes are associated with lower risk.

Conclusions Fruit, vegetables and legumes associated with a moderately lower risk of mortality, but not CVD Benefits appear to reach a maximum versus mortality at 3 to 4 daily servings (375 g) Raw vegetables appear to be more protective than cooked vegetables A balanced diet of >3-4 daily servings fruit, vegs. and legumes is associated with lower mortality Fruit, vegetables and legumes strongly associated with a moderately lower risk of mortality, but not CVD - consistent by region -substantial attenuation of the risk estimates is found w/ adjustment for confounders – possibility of residual confounding exists (protection may be over estimated) – however, we did everything possible to minimize this. Benefits appear to reach a maximum versus mortality at 3 to 4 daily servings (375 g) Raw vegetables appear to be more protective than cooked vegetables A balanced diet of >3-4 daily servings fruit, vegs. and legumes is associated with lower mortality

EXTRAS

Total fruit, vegetable and legume intake vs. mortality 1.2 1.0 HR 0.8 0.6 1 2 3 4 5 6 7 8 9 Servings/day

Mean contribution of fruit type to total fruit intake

Mean contribution of vegetable type to total vegetable intake Excluding China (N=42,152) because FFQ did not collect vegetable intake by type

Myocardial Infarction Risk of MI and stroke by total fruit, vegetable and legume intake (servings/day) Myocardial Infarction Stroke N=9,082 N=19,032 N=35,128 N=24,485 N=14,849 N=9,790 N=6,945 N=4,857 N=11,163 P-trend=0.20 P-trend=0.71

Risk of CV and non-CV mortality by total fruit, vegetable and legume intake (servings/day) P-trend=0.057 P-trend=0.0038

Risk of total mortality by tertiles of total fruit, vegetable and legume intake (servings/day), by region

PURE: 195,000 from 1000 communities in 26 countries from 5 continents